In vitro and in vivo models are being developed for testing the efficacy of test compounds for controlling the growth of microsporidia. The in vitro model utilizes Encephalitozoon intestinalis and Vittaforma corneae (as a surrogate for Enterocytozoon bieneusi, the most common microsporidian infecting humans, but which can not be grown in culture). Three groups of compounds have been found to be effective in controlling microsporidia including, a) the benzimidazoles which inhibit the assembly of microtubules, b) fumagillin and its analogue, TNP 470, which are tumor growth inhibitors, and c) lufenuron, a chitin assembly inhibitor. Of the benzimidazoles, albendazole was most effective with MIC50 values of 8.0 ng/ml (+/ 4.23) and 55.0 ng/ml (+/ 7.07) for Enc. intestinalis and V. corneae, respectively. Fumagillin and TNP 470 were equally effective with fumagillin expressing MIC50 values of 0.515 ng/ml (+/ 0.002) and 0.81 ng/ml (+/ 0.014) for Enc. intestinalis and V. corneae, respectively, and TNP 470 expressing MIC50 values of 0.35 ng/ml (+/ 0.212) and 0.375 ng/ml (+/ 0.106) respectively. If administered in culture for two weeks or more, these drugs are parasitocidal in that no infectious microsporidia are detected. Additional compounds that are demonstrating efficacy against these microsporidia include nitazoxanide, a natural plant alkaloid named berberine, and atovaquone. Studies also are underway to develop animal models of microsporidia for testing drug activities. Presently, SIV infected can be infected intravenously with Encephalitozoon cuniculi, Encephalitozoon hellem, and Enc. intestinalis. Lesions are primarily seen in the liver, kidneys, and small intestine, and parasite shedding is detected in the urine and stool. Murine models are being further evaluated for E. intestinalis and V. corneae, with plans to develop a model for Ent. bieneusi